Day: 02/12/2023

Fiber, a True Superfood

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Hundreds of studies done in the last 15 years have shown how your microbiome (gut bacteria) helps you to retain your health (Aliment Pharmacol Ther, 2019;49(5):506-515), and that what you eat determines the ratio of healthful to harmful types of bacteria in your colon. These bacteria govern your immune system that determines, to a large degree, what diseases you will develop and how long you will live. Your colon bacteria appear to determine your chances of suffering from obesity, diabetes, heart attacks, strokes, cancers and many other diseases.

Your colon contains trillions of bacteria that help to control your digestion and just about everything that happens in your body. What you eat determines the types of bacteria that thrive in your gut. Fiber in plants promotes the growth of the healthful bacteria, so when you eat lots of plants, you will build a large colony of these bacteria. The healthful bacteria convert the soluble and fermentable types of fiber into short chain fatty acids (SCFAs) that have immense health benefits (J Lipid Res, Sept 2013;54(9):2325-40). SCFAs can help to:
• reduce inflammation
• lower high levels of blood sugar, cholesterol and blood pressure
• reduce hunger
• cause your intestinal linings to produce beneficial mucus that lines your colon to help prevent the harmful bacteria from penetrating there

How Much Fiber Do You Need?
Eating a lot of the foods that contain soluble fiber helps the good bacteria to overgrow the bad ones by depriving them of oxygen (Science, Aug 11, 2017:357(6351):548-549). Soluble fiber is found in varying amounts in vegetables, fruits, beans, whole grains, nuts and other edible seeds. The more of these foods you eat, the higher your levels of SCFAs (Gut, Nov 2016;65(11):1812-1821). Insoluble fiber is usually not broken down in the colon, so it passes through your digestive tract intact and helps to move undigested food through your colon to help prevent and treat constipation. See Soluble and Insoluble Fiber

Less than five percent of North Americans meet the Institute of Medicine’s recommended fiber intake of 25 grams for women and 38 grams for men. The average person gets only 16 grams of fiber per day. A review of 185 prospective studies and 58 clinical trials shows that people who take in the most fiber had a 15–30 percent decrease in deaths during the study periods, reduced rates of heart attacks, strokes, diabetes, and colorectal cancer, as well as less high blood pressure, high cholesterol or obesity (Lancet, Feb 2, 2019;393(10170):434-445). The hunter-gatherer Hadza tribes in Tanzania take in up to 150 grams per day of fiber, which is more than ten times what North Americans eat, and suffer no apparent ill effects (PLoS Biology, 2018; 16(11):e2005396).

Lifestyle Changes Can Improve the Bacteria in Your Colon
Your current diet determines which bacteria live in your gut. Even if your colon is full of harmful bacteria, you can change your colon bacteria by switching to a high-fiber diet that includes a wide variety of plants.

Older people who live in long-term-care facilities and eat a very low-fiber diet lack healthful diversity and growth of the bacteria in their colons and have very high markers of inflammation and frailty (Nature, 2012;488:178–184).

Another study followed a large number of people who moved from Thailand, where they ate lots of plants, to Minnesota where they switched to the typical Western Diet of fast food, sugared drinks and foods, meat, and fried foods. Within just a few weeks they lost their advantage of diverse and healthful colon bacteria (Cell, Nov 1, 2018;175(4):962-972.e10).

Giving high doses of antibiotics commonly used to treat hospitalized patients with very serious infections did not kill all of their gut bacteria, but caused an immediate drop in healthful bacterial colon diversity. Clostridium species that had not been found before the patients received antibiotics appeared in large amounts. Clostridia overgrowth is responsible for many difficult-to-treat infections that can follow the use of antibiotics

Protein Loading May Increase Risk for Heart Attacks

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Athletes in sports requiring great strength who eat a very-high protein diet increase their risk for dying at a young age of heart attacks, even though protein loading does not grow larger muscles.

A study by Stanley Hazen at the Cleveland Clinic has identified a chemical produced by human colon bacteria called phenylacetylglutamine (PAG) that causes clots that can cause heart attacks (Cell, March 5, 2020). This could explain why young body builders and weightlifters have such a high rate of heart attacks, even though the recent literature shows that strength training and having large muscles helps to prevent heart attacks (Med & Sci in Sports & Ex, March 2019;51(3):499-508). There is no question that the anabolic steroids that many weightlifters take to help them grow larger muscles markedly increase risk for forming plaques in arteries and the chances of dying from heart attacks (Circulation, 2017;135:1991–2002). However, those who eat the most meat are also at high risk for heart attacks (Arch Intern Med, 2012;172(7):555-563), and eating lots of red meat increases risk for type 2 diabetes (Am J Clin Nutr, 2011;94(4):1088-1096) and cancer (Nutr Cancer, 2009;61(4):437-446). Furthermore, taking in large amounts of whey protein from milk has been associated with increased heart attack risk (American J Emerg Med, 2017;35:664).

How Can Protein Loading Cause Heart Attacks?
Human protein is made up of 21 building blocks called amino acids. When you eat dietary sources of protein, your intestinal enzymes separate the protein into amino acids and you absorb singles and chains of amino acids into your bloodstream. However, when you overload on protein from plants or animals, some of the amino acids are not absorbed in the upper intestines and pass to your colon. In particular, one unabsorbed amino acid, phenylalanine, is then broken down by colon bacteria to form phenylacetic acid, which passes to the liver, where it is converted to phenylacetylglutamine (PAG). PAG causes clots to form anywhere in your body to cause heart attacks, strokes and lung clots. Since absorption of large amounts of phenylalanine occur in the colon only when you overload on protein, this explains why eating too much protein can cause heart attacks.

The researchers also demonstrated that PAG causes clots through the sympathetic nervous system that produces adrenalin. Taking drugs called beta blockers that block adrenalin from the sympathetic nervous system helps to prevent clotting and heart attacks.

My Recommendations
This is a potential Nobel Prize for Dr. Stanley Hazen, if further research by other investigators supports his brilliant discovery that protein loading from meat or plants increases production by colon bacteria of a chemical called PAG that is known to cause clots that cause most heart attacks and strokes.

Scientists have known for many years that people who eat large amounts of meat are at increased risk for dying prematurely from heart attacks, diabetes and certain cancers, but they have blamed the fat, saturated fat and cholesterol, which are all components of high-protein foods. Dr. Hazen’s research suggests that the protein itself may be the culprit. While we await further studies, I recommend avoiding the very high protein diets. You do not need a lot of extra protein to build muscle.

The 15 Most Filling Healthy Foods

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The ‘Holy Grail’ of eating well may be to consume healthy foods that leave you feeling full and satisfied after eating. This is perhaps the best way to both eat the right amount of food for your body and to avoid filling up on nutrient-less “junk” foods.

In fact, foods that fill you up and satisfy hunger have multiple benefits, going far beyond appetite control.

So without further ado, here’s a closer look at the benefits of feeling full after eating, what makes certain foods more satisfying, and the most filling foods straight from nature.

The Benefits of Feeling Full & Satisfied

Why is it beneficial to feel full and satisfied after eating?

The most straightforward answer is that feeling full helps keep your appetite in line. If you’re eating foods that leave you hungry again an hour or two later, it’s easy to reach for an unhealthy snack. But if you feel nicely filled up for several hours after eating, it’s much easier to fight temptation and stick to a healthy eating plan.

Of course, one of the most obvious further benefits of this is weight management.

Hunger is a signal to your body that it’s time to eat. When it hits, you are likely to not only eat more than you should, but also to reach for whatever is closest to hand— healthy or not. This can quickly sabotage even the best weight loss or maintenance plan.

However, feeling full goes far beyond simply your weight.

In general, the most filling foods are also dense in nutrients, especially the plant-based ones. Most processed foods will leave you empty after a short period of time and don’t provide your body with much that’s good.

By choosing healthy foods that fill you up, your body gets the nutrition it needs, and cravings tend to decrease as a bonus. (After all, your body is after nutrients, though we often judge food by how it tastes. If it gets satisfied, it won’t be sending you signals to keep eating.)

And as a final note, feeling full also helps the people around you by keeping you from becoming “hangry”— irritable or bad-tempered from hunger!

What Makes a Food Filling?

the most filling foods

The technical term for feeling full and satisfied after eating is satiety. Foods with a higher satiety index are more filling, while those with a lower score are less filling.

You can get a general idea of which foods will help you stay full for longer by looking at a few characteristics:

  • Fiber Content— Fiber is greatly lacking in the standard western diet, which is unfortunate because it’s very filling. It draws water into your digestive tract as it moves through, which helps create a sensation of fullness. Studies show that it may slow digestion as well, further increasing satiety. Fiber also normalizes bowel movements, supports your gut microbiome, and may even help you live longer!
  • Protein— Protein is a macronutrient that increases satiety and helps control hunger. Researchers believe it has this effect because it takes longer to digest than carbohydrates but also because it alters levels of satiety-related hormones like ghrelin and glucagon-like peptide 1.
  • Low Energy Density— Foods with a low energy density tend to be high in water and fiber but low in fat and calories. Obviously, fat is an important part of the diet, so you don’t want to restrict yourself to these foods all the time, but they are generally more filling than high energy density foods.

To give you specific options to choose from, here is a list of nature’s most filling vegetables, fruits, grains, and more. As always, consider choosing organic varieties of these foods, especially those whose skin / outer layer you consume.

The Most Filling Foods Straight from Nature

Potatoes

Potatoes have been regarded as unhealthy in the past, but they are actually extremely nutritious— and very filling.

Loaded with nutrients like potassium, vitamin C, magnesium, manganese, phosphorus, and B vitamins, potatoes have decent amounts of fiber and water as well as a moderate amount of protein. When compared with 37 other foods in one study, potatoes ranked the highest for satiety.

Potatoes also contain something known as resistant starch that feeds the good bacteria in your gut and may help with blood sugar control.

Always keep the skin on your potatoes, since this is where much of the nutrition — including most of the fiber and minerals — are found.

Oats/Oatmeal

oatmeal anti-aging

Oats are one of the most filling grains due to their high soluble fiber content. Studies have found that oatmeal, in particular, increases satiety and decreases appetite for hours after eating it.

A particular soluble fiber in oats, beta glucan, seems to be mostly responsible for these effects. The exact way it works is still being researched, but there is some indication that it may stimulate the release of satiety hormones. As an added benefit, it also supports heart health and has shown anti-diabetic properties.

Consider opting for steel cut oats, which are minimally processed, provide more nutrients than other oat varieties, and are particularly high in fiber.

Avocados

Is there anything avocados can’t do? They are one of the most nutritious fruits you can eat and one of the most filling foods as well.

Even though avocados are rich in fat (which tends to be less filling), they are also packed with fiber— almost 14 grams per avocado! This alone would help you to feel full and satisfied after eating, but avocados have an additional boost from 4 grams of protein per fruit.

Eating an avocado a day also gets you loads of nutrients like vitamin C, vitamin E, vitamin K, B vitamins, magnesium, and potassium. It’s no wonder this superfood can fight inflammation, boost gut health, and much more!

Chickpeas

Chickpeas are a great example of a high fiber food that’s also rich in plant-based protein. This combination means that chickpeas are slowly digested by your body, keeping you feeling full for longer.

Along with this fiber-protein combination, chickpeas are absolutely packed with minerals, plus a few vitamins. Not only can you make them a part of satisfying meals, hummus as an afternoon snack has been shown to increase fullness and reduce appetite. One way to fight those afternoon cravings!

Apples

Apples are a very underrated fruit. They are an excellent source of fiber, particularly a soluble type known as pectin that helps to slow down digestion and increase feelings of fullness.

In fact, apple pectin has shown many benefits beyond just filling you up. It feeds the good bacteria in your gut, appears to help with blood sugar control, aids certain gastrointestinal problems, and may even fight cancer.

Keep the skin on apples for maximum fiber and nutrients, and eat regularly for health and a satisfied appetite!

Almonds (& Other Nuts)

Nuts are another example of a high protein plant food. This protein, combined with a decent amount of fiber, is what makes them one of the most filling foods and a particularly good snack food.

There are many healthy nuts to choose from: pistachios, walnuts, pecans, etc.

However, almonds really stand out as an all-around “super nut”. Studies confirm that they can make you feel full and satisfied after consuming them, and they also have an excellent nutrient content. Just a handful of almonds is rich in manganese, magnesium, and vitamin E as well as powerful antioxidants that protect your body from inflammation and disease.

Quinoa

Quinoa — technically a seed but classified as a whole grain — is gluten-free, naturally rich in fiber ,and a source of complete protein (meaning it contains all essential amino acids). As you know by now, this combination sets it up as a food to keep you feeling full.

When it comes to fiber content, quinoa beats out many other grains and comes in at about 5 grams of fiber per cup. It’s also rich in essential minerals like iron, zinc, magnesium, and manganese as well as folate and vitamin E.

To stay filled up for even longer, pair quinoa with a denser food like avocado.

Beans (& Other Legumes)

the most filling foods beans

Chickpeas aren’t the only legume that will make you feel nice and full after eating them. Most legumes have that ideal combo of fiber and protein that promotes satiety.

Beans are the perfect example of this. They pack in lots of fiber, protein, and complex carbs as well as nutrients like iron, potassium, and folate. If you find them difficult to digest (as many do), soak them before cooking thoroughly. This reduces lectin content— the cause of bean “discomfort”.

Other filling legumes include lentils and peas, which also rate high on the satiety scale.

Broccoli & Other Cruciferous Veggies

Cruciferous vegetables have numerous outstanding health benefits, and you can add them to the most filling foods list. They are loaded with fiber and have a high water content, both of which take up space in your stomach and make you feel full.

Broccoli perhaps stands out from the rest because it has a good protein content to complement the fiber. Still, you can’t go wrong with other choices like cauliflower, Brussels sprouts, or cabbage.

No matter which cruciferous vegetable you choose, you’ll also be getting cancer-fighting compounds in every serving. Steam broccoli and related veggies for maximum nutrients and digestibility.

Bananas

Bananas are one of the more filling fruits with excellent fiber and water content. They contain resistant starch (the same type that’s in potatoes), which acts as a prebiotic and may further improve satiety.

As you may know, bananas are also an excellent source of potassium and contain a surprisingly high amount of vitamin C. The resistant starch in them has even shown promise for improving insulin sensitivity and blood sugar levels.

To make a banana more filling, pair it with a protein like nuts or nut butter. For the most resistant starch, choose slightly underripe bananas.

Berries

Berries may seem somewhat surprising as a filling food. After all, you can eat a large amount of them at one time almost like candy.

However, the high fiber and low calorie nature of berries gives them a lot of staying power when it comes to appetite. This is especially the case for berries high in pectin, which is the same fiber found in apples that can slow stomach emptying and increase feelings of fullness.

For maximum fiber content, go for blackberries or raspberries, which both check in at about 8 grams per cup. Again, pair them with a protein, like nuts, to stretch out the feeling of fullness.

Chia Seeds

Chia seeds may be tiny but they are bursting with fiber and protein. They also have a unique property that truly makes them one of the most filling foods, despite their size.

If you’ve ever soaked chia seeds, you’re already familiar with this property: the ability to pull in liquid and turn it into a gel-like substance. This is due to the high soluble fiber content of the seeds and happens in your gut, too, making you feel full.

In fact, some research shows that chia seeds can absorb up to 15 times their weight it water, which slows their passage through your digestive tract and maintains that feeling of fullness. Just a tablespoon or two a day can help keep your appetite in check.

Oranges

The same study that found potatoes had the top satiety score also ranked oranges high up. They actually had the same score as apples, likely due to their high fiber— and specifically pectin— content. Oranges have a high water content as well, which also helps you to feel full after eating them.

As you probably already know, opt for whole oranges over the juice to get all their filling fiber. You’ll also be feeding your body a great amount of immune-boosting vitamin C and anti-aging carotenoid antioxidants.

Celery

the most filling foods celery

Though you may think of celery as all fiber, it’s mostly made up of water. It does still have a very decent fiber content, though, with about 2 grams in 2 medium stalks. This water-fiber combination is what helps you to feel full after eating it, particularly because part of the fiber is in the form of pectin.

If you need even more reasons to eat celery, it contains powerful compounds like apigenin and kaempferol that have antioxidant power. Eat it with natural nut butter or guacamole to stay full for even longer.

Pears

Pears are a very high fiber fruit, coming in at 4-6 grams per medium fruit. The fiber is a combination of both soluble and insoluble types, including a good amount of pectin. This high pectin content (as you probably guessed) plays a big part in making pears a surprisingly filling food, particularly when paired with a protein.

To get the most amount of fiber, leave the skin on your pears. This will give you the added bonus of an antioxidant boost, particularly when eating red pears.

Adding in Greens for a Fullness Boost

Now that you know more about the most filling foods that nature provides, all that’s left is to add a variety to your diet to consistently feel full and satisfied after eating.

Of course, some days that’s easier said than done…

While it’s generally best to consume foods in their whole forms, you might want to consider having something like these Organic Supergreens from Paleovalley on hand for less-than-ideal days. The Supergreens mix contains several of the foods listed in this article (broccoli, cauliflower, berries, etc.) in convenient powdered form.

With about 1 gram of fiber in a tablespoon and tons of nutrients, you can add this mix to plain water, a smoothie, or any other liquid to quickly feel full.

Blood Test Predicts Which People With Amyloid Are Likely to Decline Cognitively

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Plasma p-tau217 outperformed other preclinical Alzheimer’s measures

A computer rendering of amyloid plaques on a neuron.

A blood test identified which cognitively intact people with brain amyloid pathology were most likely to deteriorate in the next 6 years, longitudinal data showed.

Compared with other measures, plasma phosphorylated tau 217 (p-tau217) best predicted decline on the modified Preclinical Alzheimer Cognitive Composite (mPACC) and the Mini-Mental State Examination (MMSE) with correlation coefficients of 0.41 and 0.34, respectively, reported Niklas Mattsson-Carlgren, MD, PhD, and Oskar Hansson, MD, PhD, both of Lund University in Sweden, and colleagues.

Baseline plasma p-tau217 also was associated with progression to Alzheimer’s dementia (HR 2.03, 95% CI 1.57-2.63, P<0.001), the researchers wrote in JAMA Neurologyopens in a new tab or window.

Alzheimer’s disease starts with a long period of amyloid-beta accumulation without symptoms. P-tau217 may help identify which cognitively unimpaired people with amyloid pathology (preclinical Alzheimer’s disease) might benefit most in clinical trials, the researchers suggested.

“It is this subgroup of individuals with preclinical Alzheimer’s disease that really needs effective disease-modifying therapies in the future,” Hansson told MedPage Today.

“We are convinced that our results have immediate implications for clinical trials evaluating novel therapies in preclinical Alzheimer’s disease populations, because the number of included participants can be substantially reduced if only including those with elevated plasma p-tau217 levels,” Hansson said.

“However, we also envision using plasma p-tau217 in preclinical Alzheimer’s disease in clinical practice in the future when a disease-modifying therapy is approved for clinical use at this early disease stage,” he added.

The researchers studied 171 people with preclinical Alzheimer’s from the Swedish BioFINDER-1 cohort and validated their findings in 52 people from the Wisconsin Registry for Alzheimer Prevention (WRAP). Mean ages were about 73 and 64, respectively. Some people in BioFINDER-1 had subjective cognitive decline, but all participants in both cohorts were objectively cognitively unimpaired.

Participants had brain amyloid pathology defined by cerebrospinal fluid (CSF) in BioFINDER-1 and by PET scans in WRAP. Besides p-tau217, other plasma measures included p-tau181, p-tau231, glial fibrillary filament protein (GFAP), and neurofilament light (NfL). Data were collected from 2010 to 2020 in BioFINDER-1 and 2011 to 2021 in WRAP.

Primary outcomes were MMSE and mPACC scores over a median of 6 years (range 2-10 years). Both tests measure global cognition; the mPACC also assesses episodic memory and timed executive function.

The researchers adjusted models for age, sex, years of education, apolipoprotein E ε4 (APOE4) allele status, and baseline cognition. They derived cognition slopes using linear regression models with cognitive score as the outcome and time as the predictor, and tested combinations of covariates and biomarkers.

Adjusting for covariates, most biomarkers were associated with mPACC slopes, and all biomarkers except plasma p-tau231 were associated with MMSE slopes. Plasma p-tau217 was the strongest biomarker to predict cognitive decline on both the mPACC (R2 0.41 vs 0.23 for a covariates-only model, P<0.001) and the MMSE (R2 0.34 vs 0.04 for the covariates-only model, P<0.001) in BioFINDER-1. Similar patterns emerged in WRAP.

Sample sizes were reduced in hypothetical clinical trials enriched for individuals with elevated plasma p-tau 217. In clinical trial simulations using mPACC slopes as the outcome in BioFINDER-1, relative sample sizes — compared with including all eligible participants — were 79% when including the three highest quartiles of baseline plasma p-tau217, 55% when including the two highest quartiles, and 42% when including the highest quartile. Similar results were seen using MMSE slopes and were validated in WRAP.

The findings complement other data about p-tau217, which has shown strong diagnostic performancesopens in a new tab or window for Alzheimer’s disease and has discriminated Alzheimer’sopens in a new tab or window from other neurodegenerative diseases and normal cognition. Recent trials, including the TRAILBLAZER-ALZ study of donanemab for early Alzheimer’sopens in a new tab or window, have included plasma p-tau217 as a metric.

The study has several limitations, Hansson and colleagues acknowledged. Plasma p-tau217 has been associated with both amyloid and tau accumulation. In this study, tau PET was not assessed and the extent to which it was linked with high plasma p-tau217 was unknown.

“However, in cognitively unimpaired individuals, tau PET uptake is usually mild and not readily detectable at the individual level, although there have been group-level increases and associations with future cognitive decline,” the researchers noted.

Mushrooms Magnify Memory by Boosting Nerve Growth

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Summary: Active compounds in the edible Lion’s Mane mushroom can help promote neurogenesis and enhance memory, a new study reports. Preclinical trials report the compound had a significant impact on neural growth and improved memory formation. Researchers say the compound could have clinical applications in treating and preventing neurodegenerative disorders such as Alzheimer’s disease.

Source: University of Queensland

Researchers from The University of Queensland have discovered the active compound from an edible mushroom that boosts nerve growth and enhances memory.

Professor Frederic Meunier from the Queensland Brain Institute said the team had identified new active compounds from the mushroom, Hericium erinaceus.

“Extracts from these so-called ‘lion’s mane’ mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells,” Professor Meunier said.

“Pre-clinical testing found the lion’s mane mushroom had a significant impact on the growth of brain cells and improving memory.

“Laboratory tests measured the neurotrophic effects of compounds isolated from Hericium erinaceus on cultured brain cells, and surprisingly we found that the active compounds promote neuron projections, extending and connecting to other neurons.

“Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain.”

This shows the lion mane mushrooms
Researchers found lion’s mane mushroom improved brain cell growth and memory in pre-clinical trials.

Co-author, UQ’s Dr Ramon Martinez-Marmol said the discovery had applications that could treat and protect against neurodegenerative cognitive disorders such as Alzheimer’s disease.

“Our idea was to identify bioactive compounds from natural sources that could reach the brain and regulate the growth of neurons, resulting in improved memory formation,” Dr Martinez-Marmol said.

Dr Dae Hee Lee from CNGBio Co, which has supported and collaborated on the research project, said the properties of lion’s mane mushrooms had been used to treat ailments and maintain health in traditional Chinese medicine since antiquity.

“This important research is unravelling the molecular mechanism of lion’s mane mushroom compounds and their effects on brain function, particularly memory,” Dr Lee said.

The study was published in the Journal of Neurochemistry.

UQ acknowledges the collaborative efforts of researchers from the Republic of Korea’s Gachon University and Chungbuk National University.

Abstract

Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory

The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity.

Here, we purified and identified biologically new active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom, together with its hydrophobic derivative hericene A, were highly potent in promoting extensive axon outgrowth and neurite branching in cultured hippocampal neurons even in the absence of serum, demonstrating potent neurotrophic activity.

Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA-12 only partly prevented the NDPIH-induced neurotrophic activity, suggesting a potential link with BDNF signaling. However, we found that NDPIH activated ERK1/2 signaling in the absence of TrkB in HEK-293T cells, an effect that was not sensitive to ANA-12 in the presence of TrkB.

Our results demonstrate that NDPIH acts via a complementary neurotrophic pathway independent of TrkB with converging downstream ERK1/2 activation. Mice fed with H. erinaceus crude extract and hericene A also exhibited increased neurotrophin expression and downstream signaling, resulting in significantly enhanced hippocampal memory.

Hericene A therefore acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance.

Odontogenic Cutaneous Fistula

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A previously healthy 42-year-old woman presented to the dental clinic with a 6-month history of swelling and pain on the right side of her chin. She reported no history of chin trauma, tooth pain, or fevers but did recall injuring her right lateral incisor while playing basketball approximately 10 years before presentation. On physical examination, there was an area of skin dimpling with overlying scabbing on the right lower portion of the chin (Panel A). Palpation of the lesion caused pain and drainage of serosanguinous fluid. Intraoral examination was notable for slight discoloration of the mandibular right lateral incisor (Panel B, arrow). A radiograph of the teeth showed periapical rarefaction and osteolysis around that tooth (Panel C, asterisk). A diagnosis of odontogenic cutaneous fistula was made. Odontogenic cutaneous fistula is caused by chronic infection of the tooth root due to dental caries, periodontal disease, or tooth fracture, as was likely to have occurred in this case. The condition manifests as dimpling, a nodule, or a cyst on the chin, jaw, or elsewhere on the face. Misdiagnosis may occur because of the variable appearance and possible lack of dental symptoms. In this case, a root canal was performed, and at the 4-month follow-up, the fistula had healed.

Source: NEJM

Tuberculous Optochiasmatic Arachnoiditis

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A 29-year-old man presented to the emergency department with a 1-week history of headache and blurry vision. Six weeks earlier, he had received a diagnosis of gastrointestinal tuberculosis and had begun antituberculosis therapy. Physical examination was notable for nuchal rigidity, papilledema, and a relative afferent pupillary defect on the right side. Ophthalmologic evaluation revealed visual acuity of 20/200 in the left eye and only light perception in the right eye. Magnetic resonance imaging of the head revealed multiple ringlike enhancing lesions near the optic chiasm, optic tracts, and perimesencephalic and suprasellar cisterns (see image). Cerebrospinal fluid analysis showed lymphocytic pleocytosis, and nucleic acid amplification testing identified Mycobacterium tuberculosis. A diagnosis of tuberculous optochiasmatic arachnoiditis was made. Tuberculous optochiasmatic arachnoiditis is a complication of tuberculous meningitis in which exudates cause inflammation of the arachnoid of the optic nerve and chiasm, which can result in vision loss. In this patient, the development of this condition was thought to be a paradoxical reaction to antituberculosis therapy that resulted in the development of new lesions. Treatment with dexamethasone was initiated, and the antituberculosis therapy was continued. At a 3-month follow-up visit, the patient’s symptoms had abated.

Source: NEJM

Lobar or Sublobar Resection for Peripheral Stage IA Non–Small-Cell Lung Cancer

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Abstract

Background

The increased detection of small-sized peripheral non–small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.

Methods

We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions.

Results

From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group.

Conclusions

In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures.

Source: NEJM